University of Namur, Institute of Life, Earth & Environment, Research Unit in Environmental and Evolutionary Biology, 61 rue de Bruxelles, B-5000 Namur, Belgium.
University of Namur, Institute of Life, Earth & Environment, Research Unit in Environmental and Evolutionary Biology, 61 rue de Bruxelles, B-5000 Namur, Belgium.
Aquat Toxicol. 2018 Dec;205:89-99. doi: 10.1016/j.aquatox.2018.10.006. Epub 2018 Oct 13.
Because of their intrinsic biological activity and ubiquitous environmental occurrence, human pharmaceutical compounds have received increasing attention from health and environmental agencies. In the present study, all-female juvenile rainbow trout (Oncorhynchus mykiss) were exposed to environmentally-realistic concentrations of a mixture of nonsteroidal pharmaceuticals for 42 days, and the effects on plasma levels of sex-steroids and the expression of genes encoding key proteins involved in ovarian development were assessed. Paracetamol, carbamazepine, diclofenac, irbesartan and naproxen were selected, as these have been detected in the Meuse River in Belgium. Fish were exposed to three concentrations of the mixture including the environmental concentration, 10- and 100-times the environmental concentration. Plasma levels of sex-steroid hormones, particularly 11-ketotestosterone, increased in a concentration-dependent way in exposed females. In addition, some key genes involved in ovarian steroidogenesis were significantly overexpressed after 7 days of exposure, such as key genes involved in the maintenance of the ovary. The steady-state mRNA level of genes implicated in germ cell fate were especially affected, such as that of foxl3 which increased by 5 fold at the highest concentration of the mixture. In conclusion, this study highlights that combined occurrence of common pharmaceutical drugs at concentrations present in surface water environments may act as endocrine-disrupting compounds in rainbow trout.
由于其内在的生物活性和广泛的环境存在，人类制药化合物受到了健康和环境机构越来越多的关注。在本研究中，全雌幼年虹鳟（Oncorhynchus mykiss）暴露于非甾体药物混合物的环境现实浓度下 42 天，并评估了对血浆中性别类固醇水平和参与卵巢发育的关键蛋白编码基因表达的影响。选择了对乙酰氨基酚、卡马西平、双氯芬酸、厄贝沙坦和萘普生，因为这些药物已在比利时的默兹河被检测到。鱼暴露于混合物的三个浓度中，包括环境浓度、环境浓度的 10 倍和 100 倍。暴露的雌性鱼类中的性类固醇激素水平，特别是 11-酮睾酮，以浓度依赖的方式增加。此外，卵巢类固醇生成中涉及的一些关键基因在暴露 7 天后显著过表达，如维持卵巢的关键基因。涉及生殖细胞命运的基因的稳定 mRNA 水平受到特别影响，例如，在混合物的最高浓度下，foxl3 基因增加了 5 倍。总之，这项研究强调了在地表水环境中存在的常见药物的共同存在可能会对虹鳟鱼产生内分泌干扰作用。
